Trace elements such as zinc are essential components of enzymes and proteins. In natural foods, zinc is generally tightly bound to macromolecules. We hypothesize that low molecular weight substances of dietary origin, or present in gastrointestinal secretions, are the vehicles for intestinal transport of zinc, through the formation of absorbable organometallic complexes. Appropriate absorption is particularly important early in life, when a lack of adequate supplies of vital nutrients may have long lasting consequences, and when childhood diseases may affect normal absorption. Our proposed research will focus on zinc chelates formed by some amino acids, dipeptides and organic acids known to, or estimated to form complexes with the lowest dissociation constants. These complexes are the ones most likely to penetrate the enterocyte by carrier mediated mechanisms and by solvent drag. We intend to perform quantitative absorption studies to determine the kinetics of the translocation processes operating in different areas of the gut, using the rat as our experimental species. The procedures will include open loop perfusions of the test solutions in anesthetized rats, everted intestinal rings and brush border membrane vesicles, plus separative techniques. This may enable us to assess the role of the brush border surface and the basolateral membrane of the absorptive cells on zinc uptake, and determine, with histochemical techniques, whether zinc is localized in particular compartments during its transport. We will also assess the interactions between macronutrients and zinc, and their effects on zinc absorption. We will study the uptake of zinc by the small intestinal mucosa under the following conditions: [a] in well nourished rats; [b] following the effects of chronic diarrhea; [c] under the influence of a deconjugated bile salt, which reflects the consequence of bacterial proliferation. The animal models to be utilized have already been tested in our own and other laboratories. Our data are expected to provide detailed information on the physiology of the luminal phase of zinc absorption in normal conditions, and in pathologic situations which frequently present early in life and which have a worldwide public health impact. Our findings may ultimately be used in the improvement of infant formulae, as well as in the preparations of dietary mineral supplements to alleviate nutritional deficits in children with conditions such as failure to thrive and diarrhea.
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